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Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
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Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
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Muscarinic receptor antagonists, also known as antimuscarinic agents, are a class of bronchodilators used to treat asthma, although they are more commonly used to treat COPD. They work by inhibiting the action of acetylcholine (ACh), a neurotransmitter, on muscarinic receptors found in the airways.
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Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
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Cholinergic antagonists bind to cholinergic receptors and limit the effects of acetylcholine and other cholinergic agonists. Based on the specific cholinergic receptor affinity, these antagonists are classified as muscarinic or nicotinic. Anticholinergics interrupt parasympathetic innervations while sympathetic innervations remain uninterrupted. Muscarinic antagonists are also called 'muscarinic antagonists', 'antimuscarinics', or 'parasympatholytics'. Nicotinic...
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Cholinergic antagonists—such as antimuscarinics—are available in oral, topical, ocular, parenteral, and inhalational formulations. Most antimuscarinics are oral formulations,  while scopolamine is available as a topical patch, and ipratropium and tiotropium are available as inhalation aerosols or powders. Atropine, tropicamide, and cyclopentolate are topically instilled in the eye. Most antimuscarinics are lipid-soluble and readily absorbed from the gastrointestinal tract and...
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Smac mimetics as IAP antagonists.

Simone Fulda1

  • 1Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Komturstr. 3a, 60528 Frankfurt, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.

Seminars in Cell & Developmental Biology
|January 1, 2015
PubMed
Summary
This summary is machine-generated.

Inhibitor of Apoptosis (IAP) proteins are highly expressed in human cancers. Small-molecule Smac mimetics targeting IAPs neutralize these proteins, promoting cancer cell death and showing promise in clinical trials.

Keywords:
CancerCell deathIAP proteinsSmac mimetic

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Inhibitor of Apoptosis (IAP) proteins are overexpressed in various human cancers.
  • IAPs play a crucial role in preventing programmed cell death (apoptosis).
  • High IAP levels contribute to cancer development and resistance to therapy.

Purpose of the Study:

  • To investigate Smac mimetics as a therapeutic strategy against cancer.
  • To evaluate the potential of targeting IAP proteins for cancer treatment.
  • To assess the preclinical efficacy and clinical translation of Smac mimetics.

Main Methods:

  • Development of small-molecule inhibitors mimicking the endogenous IAP antagonist Smac.
  • Preclinical testing in various human cancer models.
  • Clinical evaluation in Phase I/II trials.

Main Results:

  • Smac mimetics effectively neutralize IAP proteins.
  • These mimetics directly induce cancer cell death in preclinical models.
  • Smac mimetics sensitize cancer cells to cytotoxic stimuli.
  • Clinical trials demonstrate the therapeutic potential of IAP-targeted therapy.

Conclusions:

  • Targeting IAP proteins with Smac mimetics is a viable therapeutic strategy for human cancers.
  • Smac mimetics represent a promising class of anti-cancer drugs.
  • The clinical advancement of Smac mimetics highlights the success of IAP-targeted therapy.